Summary of Study ST002331

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001495. The data can be accessed directly via it's Project DOI: 10.21228/M8GM6Q This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study ID	ST002331
Study Title	Comprehensive characterization of putative genetic influences on plasma metabolome in a pediatric cohort
Study Summary	Background: The human exposome is composed of diverse metabolites and small chemical compounds originated from endogenous and exogenous sources, respectively. Genetic and environmental factors influence metabolite levels while the extent of genetic contributions across metabolic pathways is not yet known. Untargeted profiling of human metabolome using high-resolution mass spectrometry (HRMS) combined with genome-wide genotyping allows comprehensive identification of genetically influenced metabolites. As such previous studies of adults discovered and replicated genotype-metabotype associations. However, these associations have not been characterized in children. Results: We conducted the largest genome by metabolome-wide association study to date of children (N=441) using 619,688 common genetic variants and 14,342 features measured by HRMS. Narrow-sense heritability (h2) estimates of plasma metabolite concentrations using genomic relatedness matrix restricted maximum likelihood (GREML) method showed a bimodal distribution with high h2 (>0.8) for 15.9% of features and low h2 (<0.2) for most of features (62.0%). The features with high h2 were enriched for amino acid and nucleic acid metabolism while carbohydrate and lipid concentrations showed low h2. For each feature, a metabolite quantitative trait locus (mQTL) analysis was performed to identify genetic variants that were potentially associated with plasma levels. Fifty-four associations among 29 features and 43 genetic variants were identified at a genome-wide significance threshold p < 3.5x10-12 (= 5 x 10-8/14,342 features). Previously reported associations such as UGT1A1 and bilirubin; PYROXD2 and methyl lysine; ACADS and butyrylcarnitine were successfully replicated in our pediatric cohort. We found potential candidates for novel associations including CSMD1 and a monostearyl alcohol triglyceride; CALN1 and a triglyceride; RBFOX1 and dimethylarginine. A gene-level enrichment analysis using MAGMA revealed highly interconnected modules for ADP biosynthesis, sterol synthesis, and long-chain fatty acid transport in the gene-feature network. Conclusion: Comprehensive profiling of plasma metabolome across age groups combined with genome-wide genotyping revealed a wide range of genetic influence on diverse chemical species and metabolic pathways. The developmental trajectory of a biological system is shaped by gene-environment interaction especially in early life. Therefore, continuous efforts on generating metabolomics data in diverse human tissue types across age groups are required to understand gene-environment interaction toward healthy aging trajectories.
Institute	Boston Childrens Hospital
Last Name	Kong
First Name	Sek Won
Address	401 Park Drive, LM5528.4
Email	sekwon.kong@childrens.harvard.edu
Phone	6179192689
Submit Date	2022-10-13
Raw Data Available	Yes
Raw Data File Type(s)	mzXML
Analysis Type Detail	LC-MS
Release Date	2023-04-13
Release Version	1

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Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id	local_sample_id	Treatment
SA229785	VT_181117_M338_013	Control
SA229786	VT_181117_M338_014	Control
SA229787	VT_181028_M338_074	Control
SA229788	VT_181028_M338_073	Control
SA229789	VT_181202_M338_146	Control
SA229790	VT_181120_M338_109	Control
SA229791	VT_181028_M338_193	Control
SA229792	VT_181110_M338_224	Control
SA229793	VT_181117_M338_151	Control
SA229794	VT_181110_M338_223	Control
SA229795	VT_181028_M338_194	Control
SA229796	VT_181202_M338_145	Control
SA229797	VT_181120_M338_110	Control
SA229798	VT_181119_M338_103	Control
SA229799	VT_181013_M338_193	Control
SA229800	VT_181013_M338_194	Control
SA229801	VT_181202_M338_176	Control
SA229802	VT_181202_M338_175	Control
SA229803	VT_181106_M338_230	Control
SA229804	VT_181116_M338_061	Control
SA229805	VT_181116_M338_062	Control
SA229806	VT_181031_M338_212	Control
SA229807	VT_181117_M338_152	Control
SA229808	VT_181031_M338_211	Control
SA229809	VT_181022_M338_248	Control
SA229810	VT_181022_M338_247	Control
SA229811	VT_181119_M338_104	Control
SA229812	VT_181013_M338_164	Control
SA229813	VT_181127_M338_235	Control
SA229814	VT_181127_M338_236	Control
SA229815	VT_181124_M338_080	Control
SA229816	VT_181124_M338_079	Control
SA229817	VT_181016_M338_056	Control
SA229818	VT_181212_M338_247	Control
SA229819	VT_181212_M338_248	Control
SA229820	VT_181119_M338_140	Control
SA229821	VT_181123_M338_175	Control
SA229822	VT_181119_M338_139	Control
SA229823	VT_181214_M338_116	Control
SA229824	VT_181214_M338_115	Control
SA229825	VT_181016_M338_055	Control
SA229826	VT_181021_M338_230	Control
SA229827	VT_181101_M338_085	Control
SA229828	VT_181101_M338_086	Control
SA229829	VT_181203_M338_152	Control
SA229830	VT_181203_M338_151	Control
SA229831	VT_181106_M338_229	Control
SA229832	VT_181130_M338_205	Control
SA229833	VT_181130_M338_206	Control
SA229834	VT_181030_M338_164	Control
SA229835	VT_181021_M338_229	Control
SA229836	VT_181030_M338_163	Control
SA229837	VT_181119_M338_014	Control
SA229838	VT_181119_M338_013	Control
SA229839	VT_181013_M338_163	Control
SA229840	VT_181026_M338_194	Control
SA229841	VT_181012_M338_044	Control
SA229842	VT_181012_M338_067	Control
SA229843	VT_181012_M338_043	Control
SA229844	VT_181209_M338_146	Control
SA229845	VT_181209_M338_145	Control
SA229846	VT_181012_M338_068	Control
SA229847	VT_181122_M338_037	Control
SA229848	VT_181211_M338_199	Control
SA229849	VT_181211_M338_200	Control
SA229850	VT_181028_M338_206	Control
SA229851	VT_181028_M338_205	Control
SA229852	VT_181122_M338_038	Control
SA229853	VT_181121_M338_092	Control
SA229854	VT_181121_M338_091	Control
SA229855	VT_181011_M338_038	Control
SA229856	VT_181031_M338_151	Control
SA229857	VT_181011_M338_037	Control
SA229858	VT_181209_M338_194	Control
SA229859	VT_181209_M338_193	Control
SA229860	VT_181031_M338_152	Control
SA229861	VT_181106_M338_037	Control
SA229862	VT_181108_M338_181	Control
SA229863	VT_181108_M338_182	Control
SA229864	VT_181120_M338_080	Control
SA229865	VT_181120_M338_079	Control
SA229866	VT_181106_M338_038	Control
SA229867	VT_181124_M338_217	Control
SA229868	VT_181124_M338_218	Control
SA229869	VT_181209_M338_079	Control
SA229870	VT_181209_M338_080	Control
SA229871	VT_181113_M338_194	Control
SA229872	VT_181113_M338_193	Control
SA229873	VT_181111_M338_230	Control
SA229874	VT_181103_M338_013	Control
SA229875	VT_181103_M338_014	Control
SA229876	VT_181116_M338_146	Control
SA229877	VT_181026_M338_193	Control
SA229878	VT_181116_M338_145	Control
SA229879	VT_181119_M338_110	Control
SA229880	VT_181119_M338_109	Control
SA229881	VT_181111_M338_229	Control
SA229882	VT_181210_M338_056	Control
SA229883	VT_181106_M338_056	Control
SA229884	VT_181123_M338_211	Control